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Revista Colombiana de Cardiología

versão impressa ISSN 0120-5633

Resumo

ARISTIZABAL, Dagnóvar et al. Genetic basis of essential arterial hypertension in Colombia: advances in nine years of work. Rev. Colomb. Cardiol. [online]. 2006, vol.12, n.6, pp.409-430. ISSN 0120-5633.

Cardiovascular diseases are the main causes of disease and non-violent death in Colombia. Arterial hypertension is the most common cardiovascular disorder in our country, with a prevalence oscillating between 13% and 23% (1, 2). Given its high frequency in the adult population, arterial hypertension is a mayor risk for the development of coronary disease, as well as for cerebro-vascular and renal diseases. The causes of arterial hypertension have been investigated for more than fifty years and it has been stated that there are environmental and genetic factors that affect the response of organs such as the kidney, the brain and the cardiovascular system, which in turn provoke alterations in the arterial pressure control and chronic hypertension. Some environmental factors like excessive caloric and salt intake, overweight, psycho-social stress and significant alcohol intake raise the arterial pressure (3), which has been corroborated in our population (4). Nevertheless, little is known regarding the genetic factors implicated in the development of hypertension. Currently, the not yet clarified genetic component determines 30% to 50% of the blood pressure levels in the population (5). In order to initiate the genetic study, a medium size population was chosen. From a total of 5.720 people with ages between 18 and 65 years, 3.000 were evaluated, excluding relatives with first degree of consanguinity (1.998 subjects). A distribution curve of the arterial pressure was obtained with 1.002 non-related individuals in whom many candidate genes for hypertension were studied (6-22). It has been found that candidate genes like the angiotensinogen gene (AGT) regulates kidney function, provokes salt retention and systemic vasoconstriction (23, 24). Other genes are implicated in the molecular sodium transport in the kidney, like the WNK1 and the GNB3 (25, 28), or act in the vasculature as the beta 2 adrenergic receptor gene (29). Initially, a case control study was designed in order to compare the 10 and 90 percentiles from the arterial pressure distribution curve. The haplotypes of the M235T in the exon and two molecular variants of the promoter region of the AGT gene (A-6G; A-20C) were analyzed. 191 people were genotyped by means of the polymerase chain reaction technique (ARMS-PCR). When comparing the different genotypes for A-20C, a genetic association between the presence of hypertension with the -20AA variant of the AGT gene was found (X2; = 4,26; p < 0,05). Later, an association of the GNB3 gene that controls the sodium transport by the renal tubules was found. It showed an independent genetic effect in the presence of hypertension in obese individuals, carriers of the 825T allele of the GNB3 gene. In these individuals hypertension would develop through vascular volume expansion due to changes in the renal salt excretion. Finally, the gene of the beta 2 adrenergic receptor did not show genetic association with hypertension, but had a high frequency in our population; for this reason, its hemodynamic effect was evaluated. The presence of homozygocity in the nucleotides that determine the amino acid in the 16 gene position modifies the hemodynamic state through significant changes in the cardiac output at rest, under postural stimulation in the tilt table or under the effect of an agonist of the beta 2 receptor. After nine years exploring the genetic basis of essential hypertension in Colombia, the presence of subgroups of individuals with phenotypic differences through certain genotypes is demonstrated. Theses results open new ways in order to understand the pathophysiology of this condition in our population and are the start point for a better characterization of hypertension with preventive and therapeutic aims.

Palavras-chave : hypertension; candidate genes; polymorphism; genomic; pathophysiology; pharmacogenetics; molecular mechanisms.

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